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Completed

NCT Number: NCT00004054

Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer

RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus radiation therapy is more effective with or without combination chemotherapy for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer.

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Key information

Conditions

Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Saint John Regional Hospital, Saint John, New Brunswick, Canada

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About this study

OBJECTIVES:

  • Compare the efficacy of androgen suppression and radiotherapy with or without subsequent paclitaxel, estramustine, and etoposide, in terms of overall and disease-free survival, biochemical and local control, and freedom from distant metastasis, in patients with localized high-risk prostate cancer.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prostate-specific antigen level (≤ 10 ng/mL vs 11-100 ng/mL), tumor stage (T1-2 vs T3-4), Gleason score (7 vs 8-10), and prior hormone use (yes vs no). Patients are randomized to one of two treatment arms.

All patients receive androgen suppression comprising a luteinizing hormone-releasing hormone (LHRH) agonist AND bicalutamide OR flutamide for 4 months. Beginning 8 weeks after the initiation of androgen suppression, all patients undergo radiotherapy once daily, 5 days a week, for 7-8 weeks. Patients who received prior androgen suppression therapy count time to radiotherapy from start date of prior hormonal therapy.

  • Arm I: Patients continue androgen suppression therapy (LHRH agonist only) for approximately 20 more months after radiotherapy is completed.
  • Arm II: Patients continue therapy as in arm I and receive chemotherapy beginning 28 days after completing radiotherapy. Chemotherapy comprises oral estramustine 3 times daily and oral etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Chemotherapy repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,440 patients will be accrued for this study within 6 years.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

DISEASE CHARACTERISTICS:

  • Histologically proven prostate cancer at high risk for relapse as determined by either of the following:
  • Prostate-specific antigen (PSA) 20-100 ng/mL and Gleason score at least 7 (any T stage)
  • Clinical stage at least T2, Gleason score at least 8, and PSA no greater than 100 ng/mL
  • Negative lymph nodes
  • No metastatic disease

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • Zubrod 0 or 1

Life expectancy:

  • Not specified

Hematopoietic:

  • White blood cell (WBC) count of at least 3,000/mm^3
  • Platelet count at least 130,000/mm^3
  • Hemoglobin at least 11.4 g/dL

Hepatic:

  • Aspartate aminotransferase (AST) no greater than 2 times upper limit of normal

Renal:

  • Creatinine no greater than 2.5 mg/dL

Other:

  • No other invasive cancer within the past 5 years except superficial nonmelanomatous skin cancer
  • No major medical or psychiatric illness that would preclude study participation
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • At least 5 years since prior chemotherapy

Endocrine therapy:

  • At least 60 days since prior finasteride for prostatic hypertrophy
  • At least 90 days since prior testosterone
  • No more than 30 days since initiation of prior pharmacologic androgen ablation for prostate cancer

Radiotherapy:

  • No prior pelvic radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery:

  • No prior radical prostatectomy
  • No prior cryosurgery for prostate cancer
  • No prior orchiectomy

Treatment and study plan

bicalutamide

Drug

Administered orally at a dose of one 50mg tablet per day. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.

Other names: Casodex

estramustine phosphate sodium

Drug

280 mg three times a day for 14 days and repeated every 3 weeks for 4 cycles

etoposide

Drug

50 mg/m^2 in divided doses b.i.d. for 14 days and repeated every 3 weeks for 4 cycles

flutamide

Drug

Administered orally at a dose of two 125 mg capsules three times a day for a total daily dose of 750 mg. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.

Other names: Eulexin

paclitaxel

Drug

135 mg/m^2 given as a 1-hour infusion (on day 2 of each cycle) and repeated every 3 weeks for 4 cycles

Luteinizing hormone releasing hormone [LHRH] agonist

Drug

Releasing hormone agonists (such as leuprolide, goserelin, buserelin, triptorelin) will be given for 4 months

radiation therapy

Radiation

Radiation will begin 8 weeks following the initiation of hormone administration: 46.8 Gy to the regional lymphatics followed by a 23.4 Gy boost to the prostate to bring the total dose to the prostate to 70.2 Gy. Daily tumor doses will be 1.8 Gy per day, 5 days per week x 7-8 weeks.

Warfarin

Drug

To keep international normalized ratio (INR) > 1.5 and < 2.5; begins with the start of chemotherapy and will be given continuously until 4 weeks after the end of the fourth cycle of chemotherapy

Other names: Coumadin

Primary outcomes

  1. Overall Survival (5-year Rate Reported)

    Time frame: From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years.

    Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 5 years.

Secondary outcomes

  1. Rate of Biochemical Failure at 5 Years

    Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

    Biochemical failure uses the American Society for Radiation Oncology (ASTRO) definition of prostate-specific antigen (PSA) rises on three consecutive occasions, with biochemical failure date being midway between the last non-rising PSA and the first rise in PSA. Time to biochemical failure is defined as time from randomization to biochemical failure, last known follow-up (censored), or death (competing risk). Biochemical failure rates are estimated using the cumulative incidence method.

  2. Rate of Local Progression at 5 Years

    Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

    Local progression is defined as documented clinical local and/or regional progression. Time to local progression is defined as time from randomization to local progression, last known follow-up (censored), or death (competing risk). Local progression rates are estimated using the cumulative incidence method.

  3. Rate of Distant Metastasis at Five Years

    Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

    Distant metastasis (DM) is defined as documented metastatic disease. Time to distant metastasis is defined as time from randomization to distant metastatic disease, last known follow-up (censored), or death (competing risk). Distant metastasis rates are estimated using the cumulative incidence method.

  4. Disease-free Survival Rate at 5 Years

    Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

    Disease-free survival (DFS) was measured from the date of randomization to the date of documentation of progression (local, distant, biochemical failure), death, or last follow-up (censored). The Kaplan-Meier method was used to estimate DFS rates.

Sponsors and collaborators

Lead sponsor

Radiation Therapy Oncology Group

Network

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

A Phase III Protocol of Androgen Suppression (AS) and Radiation Therapy (RT) vs AS and RT Followed by Chemotherapy With Paclitaxel, Estramustine, and Etoposide (TEE) for Localized, High-Risk, Prostate Cancer

Important dates

Study start
2000
Primary completion
2010
Study completion
2013
First posted
Jan 27, 2003
Registry last updated
Oct 22, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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